Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEVER-155008Cat.No.:HY-10941CASNo.:1134156-31-2分?式:C??H??Cl?N?O?分?量:556.4作?靶點(diǎn):HSP;Autophagy作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥37mg/mL(66.50mM)掃描?維碼，*"≥"meanssoluble,butsaturationunknown.運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.7973mL8.9863mL17.9727mL5mM0.3595mL1.7973mL3.5945mL10mM0.1797mL0.8986mL1.7973mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶1.請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(4.49mM);Clearsolution此?案可獲得≥2.5mg/mL(4.49mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/4www.MedChemEwww.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.49mM);Clearsolution此?案可獲得≥2.5mg/mL(4.49mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(4.49mM);Clearsolution此?案可獲得≥2.5mg/mL(4.49mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性VER-155008?種Hsp70的抑制劑，對(duì)Hsp70，Hsc70和Grp7的IC50值分別為0.5μM，2.6μM和2.6μM，對(duì)Hsp70的Kd值為0.3μM。IC50&TargetHSP70HSC70Grp780.5μM(IC50)2.6μM(IC50)2.6μM(IC50)體外研究VER-155008isaninhibitorofHsc70andHsp70,withIC50sof0.5μM,2.6μM,and2.6μMforHsp70,Hsc70andGrp7,respectively,awithaKdof0.3μMforHsp70,butshowsnoactivitiesagainstHsp90,withanIC50of>200μM.VER-155008inhibitstheproliferationofavarietyofhumancolonandbreasttumorcelllines,suchasBT474,MB-468,HCT116andHT29cells,withGI50sof10.4μM,14.4μM,5.3μM,and12.8μM,respectively.VER-155008(5-40μM)inducesclientproteindegradationinHCT116andBT474carcinomacells.VER-155008alsoinducesapoptosisinhumantumorcelllines[1].VER-155008(0.05-5μM)reversesAβ-inducedaxonaldegenerationinculturedneurons[2].VER-155008(10μMor25μM)inhibitsHsp70andsuppressestheproliferationofLNCaP95cells.VER-155008alsoreducesfull-lengthandrogenreceptor(AR-FL)andandrogenreceptorsplicevariant7(AR-V7)proteinexpression[3].體內(nèi)研究VER-155008(25mg/kg,i.v.)exhibitsplasmaclearanceinnaivefemaleBALB/cmice.VER-155008(40mg/kg,i.v.)alsoshowsrapidplasmaclearance,andreducesthetumorlevelsintheHCT116tumorbearingnudeBALB/cmice[1].VER-155008(10μmol/kg/day,i.p.)rescuesmemorydeficits,andreducesaxonalswellingassociatedwithamyloidplaquesin5XFADmice.VER-155008(89.9μmol/kg/day,i.p.)penetratesintothebrainafteradministrationin5XFADmice.VER-155008alsodecreasesamyloidplaquesandPHF-tauassociatedwithamyloidplaquesin5XFADmice[2].PROTOCOLCellAssay[2]EmbryosareremovedfromapregnantddYmouseat14daysofgestation.Cellsaretreatedwithorwithout10μMAβ25-35for3days,followedbytheadditionof0.05,0.5,or5μMVER-155008orvehiclesolution(0.1%DMSO)for4days.TheAβ25-35isincubatedat37°Cfor4dayspriortotreatmenttofacilitateaggregation.Thecellsarefixedwith4%paraformaldehydeandimmunostainedat4°Cfor24hwithantibodiesagainsttheaxonalmarker,mousephosphorylatedneurofilamentheavysubunit,andagainstthe2/4www.MedChemEwww.MedChemEneuronalmarker,rabbitmicrotubule-associatedprotein2.AlexaFluor488-conjugatedgoatanti-mouseIgG(1:400)andAlexaFluor568-conjugatedgoatanti-rabbitIgG(1:400)areusedassecondaryantibodies.Fluorescenceimages(864.98μm×645.62μm)arecapturedusingafluorescencemicroscopysystem.ThelengthsofthepNF-H-positiveaxonsaremeasuredusingMetaMorphversion7.8[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalFemaleBALB/cmicearedosedintravenouslywith25mg/kgVER-155008intothelateraltailveinasaAdministration[1]solutionin10%DMSO/5%Tween80/85%saline(v/v/v).Animalsaresacrificedat5,15and30min,1,2,4and6hpostdose[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?PhytotherRes.2018Jul;32(7):1320-1331.?AmJPhysiolGastrointestLiverPhysiol.2020Jun1;318(6):G1000-G1012.?Pathogens.2021,10(3),283.?MicrobPathog.2020Nov24;104647.?DomestAnimEndocrin.2021Jan;74:106533.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MasseyAJ,etal.Anovel,smallmoleculeinhibitorofHsc70/Hsp70potentiatesHsp90inhibitorinducedapoptosisinHCT116coloncarcinomacells.CancerChemotherPharmacol.2010Aug;66(3):535-45.[2].YangX,etal.HeatShockCognate70Inhibitor,VER-155008,ReducesMemoryDeficitsandAxonalDegenerationinaMouseModelofAlzheimer'sDisease.FrontPharmacol.2018Jan30;9:48.[3].KitaK,etal.Heatshockprotein70inhibitorssuppressandrogenreceptorexpressioninLNCaP95prostatecancercells.CancerSci.2017Sep;108(9):1820-1827.McePdfHeight3/4www.MedChemEw